Nanotechnology Spotlight

Tissue engineering with cell-laden hydrogels

(Nanowerk Spotlight) The ultimate goal of tissue engineering as a medical treatment concept is to replace or restore the anatomic structure and function of damaged, injured, or missing tissue – ultimately providing doctors the ability to replace entire organs. At the core of tissue engineering is the construction of three-dimensional scaffolds out of biomaterials to provide mechanical support and guide cell growth into new tissues or organs. Experimental efforts are currently underway for tissue engineering involving virtually every type of tissue and every organ of the human body.

Hydrogels have been in development for several decades and are being used as parts in biology-based microdevices and medical diagnostic technologies, for drug delivery, and in tissue engineering. These gels are networks of water-insoluble polymer chains that are attractive for tissue engineering since their physical (i.e. mechanical strength and biodegradability) and biological properties (i.e. the biocompatibility and resemblance to the natural extracellular matrix) can be tailored to mimic tissues. Researchers have found that the encapsulation of cells within cell-laden microgels is an attractive approach for engineered tissue formation.

Researchers have now developed a technique for the self-assembly of cell-laden microgels on the interface of air and
hydrophobic solutions to fabricate three-dimensional (3D) tissue constructs with controllable microscale features.

"Our lab has previously pioneered methods of assembling gels but this work makes a great stride in this area by showing that liquid-air interfaces can be used to assemble tissue building blocks made from cell encapsulated in shape controlled microgels," Ali Khademhosseini tells Nanowerk.

Khademhosseini is an Assistant Professor at Harvard-MIT's Division of Health Sciences and Technology, Brigham and Women’s Hospital and Harvard Medical School. Together with his group and collaborators from MIT and Northeastern University, he introduces a fabrication method for creating tissue-like structures using a bottom-up self-assembly
approach in a multiphase environment (the liquid–air system).

"The high-density solution forces the lower-density hydrophilic hydrogels to remain on the surface, similar to techniques previously reported for inorganic materials," explains Khademhosseini. "We randomly placed hydrophilic, cell-laden hydrogels on the surface of high-density, hydrophobic solutions. Surface tension drove the
microgels toward each other to create tissue-like structures through aggregation. These basic thermodynamic mechanisms enabled the fabrication of centimeter-scale tissue structures from cell-laden micrometer-scale hydrogels."

He points out that the ability to create tissues with these length scales and a clinically relevant overall size suggests that this technique may be beneficial for tissue-engineering applications.

Since cell viability is a critical factor for creating robust tissue-like structures, the researchers tracked cell
viability over a one-week period to assess the feasibility of the current assembly technique for creating long-term engineered tissues.

"Viability remained above 90% on days 1 and 3 and remained at or above 85% for up to one week" says Khademhosseini. "There were no significant losses in viability throughout the process or subsequent culture, demonstrating the suitability of this technique for creating robust long-term tissue-like structure."

He notes that this technique can be used to rapidly create tightly packed tissue-like sheets with either single cell types or homogeneously distributed coculture.

"In addition, we demonstrated a hierarchical approach that can create complex multigel building blocks with precisely controlled coculture distribution to create tissue-like constructs with specific cell distribution. Even greater control over this technique can be achieved by using specific structures, such as lock-and-key assemblies, to better direct the assembly of cocultured tissues. The ability to precisely control the cell distribution within self-assembled tissue-like constructs could greatly improve engineered tissue function and morphology."

The team's goal now is to add on this work to generate more complex 3D structures as well as to merge these techniques with advances in stem cell biology to engineer transplantable tissues.